Objective:

The skin's integrity depends on precursor cells that regenerate different skin compartments. The epidermis contains keratinocyte stem cells (KSCs), while the dermis contains skin-derived precursors (SKPs), which are multipotent dermal fibroblast precursors. SKPs express specific markers including structural proteins (nestin, fibronectin, vimentin) and transcription factors (PAX3, SHOX2, SNAI1, SNAI2, SOX9, TWIST1, TWIST2). We have recently shown that the ELN gene, encoding tropoelastin, plays a crucial role in protecting cells from senescence. Given the age-dependent depletion of human skin-derived progenitor cells, this study investigated whether an anti-aging yeast extract could maintain ELN gene expression and tropoelastin protein to prevent senescence.

Methods:

SKPs were embedded into reconstructed dermal equivalent to evaluate their effect on collagen types I and elastin content by specific immuno-stainings. Treated with 1% yeast extract twice a day for 2 days before the staining. Fibroblasts were also derived from the SKP and immune-stained for collagen and elastin but also embedded into a collagen matrix induced a greater contractility of the dermal equivalents.

Results:

Treatment of SKPs in the 3D dermal model with 1% yeast extract resulted in increased pro-collagen type I (+35%) and tropoelastin (+17%) secretion. SKP-derived fibroblasts combined with regular fibroblasts in the collagen matrix demonstrated enhanced contractility of the dermal equivalents. Treatment with 1% extract for five days before introduction into the collagen matrix resulted in reduced tissue stiffness and improved elasticity.

Conclusions:

The findings indicate that SKPs and SKP-derived fibroblasts are essential contributors to dermal extracellular matrix composition. Resident SKPs represent a promising target for improving dermal constituents lost during both chronological and extrinsic aging. The yeast extract, by maintaining elastin function and modulating SKP activity, shows potential in preserving dermal integrity and homeostasis, ultimately contributing to healthier-looking skin.